The precise causes of multiple sclerosis continue to baffle the scientific community, although in general most researchers agree that a combination of genes and environmental factors appear to play a role in influencing the risk of developing MS. In those people living with MS, there is a great deal of research ongoing that’s looking at different types of exposures that can impact the course of the disease, such as the rate of relapses, severity, and progression. At AAN, a handful of researchers took to the podium to present their latest findings about the genetic and environmental factors that affect the risk of MS and play a role in modifying disease course.
Between 2 – 5% of multiple sclerosis cases emerge before the age of 18. Research into MS in children and adolescents – referred to as pediatric-onset MS – is not only important for managing the disease in youth, but can also provide insights into some of the earliest triggers and drivers of MS, with implications for understanding and treating MS across all groups. Since MS is believed to spring from a combination of specific genetic and environmental factors, invited speakers at the pediatric-onset MS seminar session presented new data exploring these factors in children and adolescents.
The conversations taking place on the third day at AAN shifted gears from the day before, placing the focus back on multiple sclerosis and exploring existing treatment strategies for people living with MS in great depth. Specific questions that were brought up include: does stopping immune-modifying treatment in those transitioning into secondary progressive MS affect persistent relapses? How commonly do clinicians switch their patients’ first treatment regimen, and why? What are the effects of specific DMTs on pregnancy outcomes in expectant mothers? Continue reading to learn some of the answers to these questions based on the most recent research findings:
One of today’s sessions placed the focus squarely on neuromyelitis optica (more recently expanded to be called neuromyelitis optica spectrum disorder, or NMOSD), a rare autoimmune disorder of the central nervous system (CNS) in which the spinal cord and/or optic nerves are attacked and damaged by specific antibodies. While far less common than MS, NMOSD can sometimes be confused with MS due to similar clinical features, although NMOSD attacks are often more severe than MS relapses. Two of the most common symptoms experienced by people living with NMOSD are inflammation of the optic nerve (called optic neuritis) which causes blurring or loss of vision in one or both eyes, and inflammation of the spinal cord (transverse myelitis), which can lead to a host of symptoms including arm and leg weakness, muscle spasms, bladder and bowel problems, and pain.
Since NMOSD and MS are fundamentally different diseases that require their own unique set of diagnostic criteria and treatment strategies, the panel brought together researchers at the forefront of NMOSD research to present their latest findings with the view to improve our understanding and management of the disease.
This year’s AAN conference is filled to the brim with programming, with sessions starting bright and early at 6:30 am and continuing well into the evening to accommodate the staggering amount of new information pouring out of the labs and clinics of researchers around the world. Headlining the MS program for Day 1 was a series of presentations about new insights into MS gained from animal and cell studies. Although modeling disease necessarily reduces the complex mechanisms underlying MS into simplified models by design, these types of studies are crucial for uncovering important clues about the genes and molecules that can trigger and/or drive MS and for rapidly screening new therapeutics with the potential to treat MS by combating harmful inflammation, repairing damage in the brain and preventing injury from occurring in the first place. The evening poster presentations were a departure from the morning’s seminar series, shifting the focus from basic laboratory research towards observations about risk factors that both influence the likelihood of developing MS and predict how the disease changes over time in those already living with MS.
This year, more than 10,000 neurologists and basic researchers from all over the world are converging on the stunningly beautiful city of Vancouver to attend the American Academy of Neurology (AAN) 68th annual meeting. Over the next few days, they’ll be resisting the temptation to hike in the nearby mountains or stroll along the winding ocean-side paths to focus on presenting their latest cutting-edge work to peers, exchange information and ideas, and form collaborations with the goal of advancing diagnosis and treatment of neurological diseases. The conference also offers intensive education programming so that clinicians can test their knowledge and stay up to date on the best clinical practices for disease treatment and management.
Although multiple sclerosis is one of many topics that will be covered at AAN alongside dementia, epilepsy, stroke, neuromuscular disorders and other neurological diseases, there are plenty of seminars and poster sessions about MS to keep the research team and I busy over the next several days. Among the topics to be covered include: new insights from animal and cell models, treatment strategies and clinical outcomes, risk factors, advanced imaging techniques, pediatric MS, and the latest findings from clinical trials. Of course, Canadian researchers will be represented in strong numbers at the various sessions – a true testament to Canada’s reputation of punching above its weight when it comes to the breadth and depth of its MS research productivity.
Be sure to check in frequently for routine updates as I distill down the scientific details into digestible summaries and key findings. Follow me on Twitter at @Dr_KarenLee (hashtag: #AANAM) for live updates as they unfold. And of course, drop any comments or questions below.
There are many reasons that people who are taking medications to help treat their multiple sclerosis might start to have second thoughts. Sometimes the side effects can be unpleasant or unbearable. Other times, the drug may not be helping them feel better or they continue to experience relapses. For some, the insurance costs may just be too high.
Until now, there has been very little information available about what happens when treatment is stopped in people with MS who are on disease-modifying therapies (DMT). Last week I came across a poster at the AAN meeting that addresses this important, unanswered question. Lead investigator Dr. Ilya Kister from the New York University (NYU) Langone Medical Centre set out to determine what happens to individuals whose disease symptoms have been stable when they decide to discontinue their DMTs. This is an important question, since identifying situations in which it is and isn’t safe for people with MS to stop taking their medications will go a long way to ensuring that disease symptoms don’t come back.
Research into the inflammatory nature of MS has led to profound progress in the treatment of the relapsing-remitting form of the disease. But this leaves us with many unanswered questions, and no treatment options, for progressive MS. Progressive MS bears severe consequences, including pronounced disability, cognitive decline, and extreme fatigue. As the need for treatments grows, so too do research efforts to help understand the onset and nature of progressive MS.
Encouraging results from one clinical trial conducted by Paris-based biotechnology company MedDay could pave the way for a novel, promising treatment option for people with progressive MS. The phase III, placebo-controlled clinical trial – dubbed MS-SPI – included 154 participants who were randomly selected to receive either MD1003 (treatment being evaluated) or a mock treatment (control) over a period of one year.
As the AAN conferences continues, so too do the updates on current and new treatments for MS. Here are some more highlights:
Efficacy and safety of alemtuzumab maintained after 4 years despite most patients not requiring additional treatment
Alemtuzumab was recently approved as a treatment for relapsing-remitting MS in Canada. It is a monoclonal antibody administered via intravenous infusion and has a dosing profile that is quite unique to the MS treatment repertoire: for the first treatment course, individuals receive one infusion of 12 mg alemtuzumab per day for five days. One year later, individuals receive one infusion per day for three days. Two pivotal phase III clinical trials for alemtuzumab in people with relapsing-remitting MS showed encouraging efficacy and safety results. Researchers have been observing individuals from these trials over time to assess the long term durability of the drug. The extension study enrolled 349 alemtuzumab-treated patients. At four years post-treatment, researchers noted that 73% of individuals treated in the first clinical trial did not require another round of alemtuzumab treatment beyond the initial two courses. As well, approximately 70% of treated patients were free of new lesions and MRI activity in years three and four, and rates of brain volume loss were reduced.
First data from long term follow up of people taking peginterferon beta-1a
Beta interferons are an approved treatment for RRMS. They work by reducing the immune response and inflammation in the central nervous system. Peginterferon beta-1a is an adaptation of interferon beta-1a. The modification allows the drug to exist in the body longer. Currently, peginterferon beta-1a is an approved MS treatment in certain countries, but is still under review by Health Canada. In a phase III clinical trial called ADVANCE, peginterferon beta-1a dosed at 125 μg every two weeks showed improvements as early as 12 weeks, with a 34% reduction in relapse rate compared to placebo. There was also a 36% reduction in people who relapsed compared to placebo. The first results of the extension phase of the study – called ATTAIN – were reported at AAN. They showed that the frequency of adverse events decreased in year 3 of treatment, with most common events being injection-site reactions and flu-like symptoms (adverse events were similar among those who received the treatment every 2 weeks versus every 4 weeks).
Two year data for emerging treatment daclizumab HYP
Daclizumab high-yield process (HYP) is a newly patented version of a drug that is commonly used to prevent rejection in organ transplantation. Daclizumab HYP prevents activation and growth of immune cells, and is administered once a month via under-the-skin injections. Results of a phase III clinical trial for daclizumab HYP – called DECIDE – demonstrated that treatment with daclizumab HYP resulted in a 45% reduction in relapse rate versus treatment with interferon beta-1a, and a 41% reduction in the proportion of people who experienced relapses. There was also a 54% reduction in the number of active lesions on MRI, and risk of disability progression was reduced by 27%. Adverse events were minor and manageable, with Infections and skin and liver-related effects more commonly seen in people treated with daclizumab HYP versus interferon beta-1a.
A large proportion of the AAN scientific program is centered on therapeutic advances. Whether it’s an early safety study, a phase II or III efficacy trial, an extension phase determining long term effects, or an observational study assessing how a drug is doing in the real world, research on the safety and benefits of treatments is critical knowledge for any conference attendee. We all have one main priority, and that is to improve the health and quality of life for people who are affected by neurological diseases, and so one of the reasons we come together at conferences like AAN is to gain information on the full repertoire of treatments.
For MS, the list of options grows each year. There are currently 10 approved disease-modifying therapies for MS (all indicated for relapsing-remitting MS) in Canada, with a number of others being tested in phase III clinical trials or submitted for Health Canada approval. As measures for treatment safety and efficacy are being discovered and refined, trials for MS drugs ensue and continue to reveal new knowledge about their benefits and risks in humans. Here are some of the first highlights reported at AAN.